Trial results for a Phase 2 study evaluating co-formulated pembrolizumab/quavonlimab (MK-1308A) in participants with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) Stage IV colorectal cancer were posted on ClinicalTrials.gov on 2026-06-08. In Cohort A, the combination achieved an objective response rate (ORR) of 45.0%, compared to 29.5% for pembrolizumab alone in that cohort.
Background
The study evaluated pembrolizumab, alone and in various combinations, for participants with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) Stage IV colorectal cancer. The trial assessed co-formulated pembrolizumab/quavonlimab (MK-1308A) among other treatments for this condition.
Trial design
The Phase 2 study (NCT04895722), known as MK-1308A-008/KEYSTEP-008, enrolled 302 participants with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) Stage IV colorectal cancer. The trial assessed the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments, including pembrolizumab alone, pembrolizumab/favezelimab, pembrolizumab/vibostolimab, and pembrolizumab plus MK-4830.
Key results
Key results for objective response rate (ORR) per RECIST 1.1, as assessed by Blinded Independent Central Review (BICR), were reported:
- In Cohort A, co-formulated pembrolizumab/quavonlimab achieved an ORR of 45.0%. This represented a difference of 15.6% (95% CI: -1.7, 32.1) compared to pembrolizumab alone, which had an ORR of 29.5% in the same cohort.
- In Cohort B, pembrolizumab plus MK-4830 demonstrated an ORR of 65.0%, a difference of 23.4% (95% CI: -3.7, 46.7) compared to pembrolizumab alone (ORR of 41.5%) in Cohort B.
- Other combinations in Cohort B included pembrolizumab/quavonlimab (ORR of 46.2%, difference of 4.6% vs. pembrolizumab alone, 95% CI: -16.9, 25.7), pembrolizumab/vibostolimab (ORR of 48.8%, difference of 7.3% vs. pembrolizumab alone, 95% CI: -14.0, 28.0), and pembrolizumab/favezelimab (ORR of 37.5%, difference of -3.8% vs. pembrolizumab alone, 95% CI: -24.4, 17.1).
A hazard ratio (HR) of 0.65 (95% CI: 0.41, 1.02) was also reported, though the specific outcome title for this analysis was not provided.
What this means
The results from this Phase 2 study indicate that several combination therapies with pembrolizumab may offer improved objective response rates compared to pembrolizumab monotherapy in participants with MSI-H or dMMR Stage IV colorectal cancer. Notably, co-formulated pembrolizumab/quavonlimab in Cohort A showed an ORR of 45.0%, a 15.6% increase over pembrolizumab alone. The combination of pembrolizumab plus MK-4830 achieved the highest ORR at 65.0% in Cohort B, representing a 23.4% difference compared to pembrolizumab monotherapy in that cohort. These findings suggest potential strategies for enhancing treatment efficacy in this patient population. The reported hazard ratio of 0.65 also points towards a positive trend, though its specific outcome is not detailed.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04895722, titled "Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (MK-1308A-008/KEYSTEP-008)", were posted on 2026-06-08 on clinicaltrials.gov.